The blood supply to the primate placenta is established by the conversion of the muscular spiral arteries into dilated funnel- shaped uteroplacental arteries whose walls are composed mainly of trophoblast cells and connective tissue. These changes are thought to accommodate the greater volume of blood flow required by the developing conceptus, and to modify the normal maternal control mechanisms of these vessels. It has been observed that pregnancies complicated by preeclampsia alone, or preeclampsia with essential hypertension, structural modification of the arterial walls is less extensive and this apparently compromises uteroplacental perfusion. The key element in the conversion of the arteries is the migration of endovascular cells, thought to be trophoblast, into the spiral arteries. The endothelium is apparently removed and this is followed by the destruction of the muscular arterial wall and its replacement by trophoblast and connective tissue. There are many gaps in our understanding of the development of the uteroplacental arteries in primates especially the cellular mechanisms by which the invasion, destruction and replacement are carried out. The long- term objective of this proposal is the characterize the process of invasion and modification of the spiral arteries in the rhesus monkey, a species with many placental anatomical similarities to the human. Specific aims are 1) to define ultrastructurally and immunocytochemically the sequence of cellular interactions between endovascular trophoblast and endothelial cells during the initial invasion of the spiral arteries; 2) to determine the cellular mechanisms by which the endovascular trophoblast removes the maternal endothelium, penetrates the walls of the arteries and destroys the smooth muscle of the tunica media. At the present time, there is little information available on how this is accomplished in primates. Careful ultrastructural descriptions will be coupled with cytochemical studies to evaluate the role of lysosomal enzymes in this process, a role suggested by studies in other species; and 3) to determine, using immunocytochemical methods, the changes in the composition of the connective tissue components of the arterial wall during the conversion of the spiral arteries to the uteroplacental arteries.